The filtration and extrusion of liposomes directed to achieving liposome preparations of uniform size are known in the art. However, filtration/extrusion rates have been low being no higher than about 12 ml/minute.
Hunt and Papahadjopolous disclose a "Method for Producing Liposomes in Selected Size Ranges" in U.S. Pat. No. 4,529,561 ("Hunt") by a filtration/extrusion process.
The Hunt process is described either as one of extruding liposomes under pressure through a "uniform-pore-size membrane" or forcing liposomes "through an orifice under pressure" The Hunt filtration-extrusion membrane process is further distinguished in Hunt from the orifice process as being performed at lower pressure. In practice, the membrane process is associated with the retention or buildup of material on the input surface of the filtration-extrusion membrane. This build up reduces flow while requiring increased driving pressure.
Suzuki et al. (U.S. Pat. No. 4,016,100) describes a liposomal preparation with a filtration step utilizing a membrane filter. In Suzuki et al. it is also noted that the liposomes are formed in a uniform size. The filtration process of Suzuki et al. further has a limited through-put capacity due to pressure limitation of membranes and the membrane occlusion that arises from material buildup on the membrane input surface.
It is an object of this invention to provide a method of extruding liposomes to provide smaller liposome sizes.
It is another object of this invention to provide a method of producing liposomes of uniform size from liposomal material.
It is an additional object of this invention to provide a high speed/high volume method of continuous size reduction of liposomes.